ONE NEUROLOGIST'S OPINION REGARDING STROKE TREATMENT AND PREVENTION

Entries from October 2005

An article reviews current knowledge regarding the potential benefits of skull surgery, to release brain pressure, in cases of large ischemic strokes.

Summary:

(As reported in The Journal of Neuroscience Nursing 2005 Aug;37(4):194-9.)

An ischemic stroke due to blockage of the middle cerebral artery (MCA) is very large and devastating.The stroke typically leads to immediate paralysis on the side opposite the stroke, as well as loss of sensation and vision on that side. It may also result in an inability to speak and understand others.The situation may worsen over the next few days, since the infarcted tissue tends to swell and push on normal brain areas.If pushed enough, previously normal brain tissue can also be damaged, suffer from further ischemia, or, in the most dramatic outcome, the lowest portions of the brain (brainstem) can be compressed, leading to death. Not everyone will experience swelling to a sufficient degree to lead to damage to other brain areas or death, but the majority of patients do.Indeed, some quote an 80% mortality for complete MCA infarctions. Younger patients tend to have even higher rates of compression since they have no brain atrophy and therefore there is less room for swelling.

Treatment for these patients with significant brain swelling includes giving solutions that tend to gradually draw water out of the brain tissue, elevating head position to improve brain venous drainage, and forcing patients to breathe rapidly (on a respirator) to constrict blood vessels (allowing for more space for brain swelling).None of these techniques tend to work all that well to improve patient outcome.

J. Tazbir et. al, in this review article, examine the still experimental surgery involving removing the skull and dura (the tough covering over the brain), which allows brain swelling to occur outside the skull, thereby avoiding brain compression. Their review suggests that decompressive surgery leads to better outcomes if used in younger patients.It also tends to better outcomes if used within 24 hours of elevations in intracranial pressure, and if used prior to signs of brainstem compression.

Commentary:

Surgical decompression seems, on the face of it, to make a lot of sense.The skull and dura are rigid.If they can be opened up temporarily, to allow brain swelling to occur, then replaced once the swelling subsides, then a potential disaster will have been averted.But other issues must be kept in mind.There is rarely a ‘good’ outcome in these cases (a counter-case example though is reported in Am J Med, 2005 Oct;118(1):1111-2).If death is averted, the patient will still be left with the effects of a large and usually devastating stroke.Also, the surgery is not minor.Large portions of the skull and dura are removed, which means that infection and other surgical risks will be at play.Consider also that the timing of surgery is a key (and thorny) issue.A surgeon doesn't want to operate on someone needlessly (that is, someone who would experience brain swelling but who wouldn’t suffer any significant damage from it) but he also doesn't want to wait until it is too late, that is, once irreversible brain damage from swelling has occurred.Given that no one can reliably predict who will experience severe enough swelling to cause a problem, no one can say with any reliability who should get the surgery.For those who are performing these surgeries, the approach has been to wait for the earliest clinical evidence of a problem, then to proceed as quickly as possible with surgery when/if this evidence is found.Clearly the utility of this procedure, and when it should be used, will need to be explored with a prospective (planned), randomized clinical trial comparing surgical to non-surgical approaches.

The American Academy of Neurology reviews the evidence and advises under what circumstances surgical correction of carotid artery narrowing (to reduce stroke) appears beneficial.

Summary:

(As published in the September 27, 2005 issue of Neurology)

Strokes are sometimes caused by carotid arteries (in the neck) becoming narrowed (stenotic) due to atherosclerosis. The stroke occurs when a blood clot, which forms at the site of the narrowing, travels into the brain, closing off a smaller artery in the brain. Sometimes the stroke occurs because the entire carotid artery becomes closed off at the site of the narrowing. A person who has recently had an ischemic stroke or a temporary stroke-like symptom (TIA), where the symptom is felt to arise from the brain area feed by the narrowed carotid artery, is said to have symptomatic carotid artery stenosis. Someone with a narrow carotid artery, but without any symptoms, is said to have asymptomatic carotid artery stenosis. In many circumstances, it is beneficial to surgically correct the region of carotid stenosis in an operation called a carotid endarterectomy. The article we are discussing reviews under what circumstances this surgery may be beneficial.

Dr. Chaturvedi et. al (on behalf of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology)performed a literature review and identified 186 studies that were felt to be methodologically sound and which addressed important questions regarding carotid endarterectomy. In their subsequent analysis and recommendations, they gave much larger weight to those studies which were methodologically superior. A few of the recommendations included in their report are as follows:

(1) Carotid endarterectomy is beneficial for patients who had a stroke or stroke-like symptom within the past 6 months and who have 70-99% carotid artery narrowing. Though the evidence is not as strong, it may also benefit those who have 50-69% narrowing, if patients have at least a 5-year life expectancy and if the surgical risk (of stroke or death) is less than 6%. (In a subgroup analysis of those in the 50-69% category, women did not experience this same benefit.)

(2) For persons with carotid artery narrowing of 60-99%, but who have not had a stroke or stroke-like symptom, it is reasonable to consider carotid endarterectomy, if they have at least a 5-year life expectancy and if the surgical risk (stroke and death) is less than 3%.

(3) For patients with severe stenosis and a recent TIA or ischemic stroke, carotid endarterectomy should be performed as soon as possible, preferably within 2 weeks of the stroke or stroke-like symptom.

Commentary:

Ever since residency I have been waiting for a 'simple' answer to the question "Who should be surgically treated for carotid artery narrowing?" Perhaps that simple answer will never come. Instead we must grapple with the rather complicated guidelines provided in this paper. Most neurologists have now come to accept that carotid endarterectomy for narrowing in the 70-99% range, in symptomatic cases, is indicated. We must remind ourselves that this applies to patients who have had symptoms within 6 months and who have some region of brain within the territory of the carotid artery that is preserved. Also, the degree of narrowing must be measured according to the same standard as used in the studies (the NASCET method of measurement).

As the degree of narrowing lowers, the benefit of surgery lessens, and the caveats multiply. For symptomatic patients with narrowing in the 50-69% range, patients should be male, be expected to live at least 5 years, and should have the surgery performed by a surgeon with a less than 6% rate of death or stroke. This advice is interesting, since it is not easy to calculate a person's life expectancy or to find out a surgeon's rate of stroke/death for the procedure! Many surgeons probably don't even know their own stroke/death rate for a particular procedure. Because of these practical difficulties, the advice could be reasonably modified as follows: a person should not undergo the procedure if he/she is known to have a disease for which the expected survival is less than 5 years. A person considering surgery should also see if he/she can find out the stroke/death rate of surgeons in the region. If that information is hard to come by, and it probably is, then a person should seek out the surgeon in his/her area who has performed the procedure the greatest number of times.

As we attempt to incorporate information from other studies, decision making is further complicated. The trials and data used as sources for the above guidelines may be too conservative, due to the benefits of early surgery. An analysis of the OXVASC trial (see my article) demonstrated a 21% chance of stroke within 2 weeks of a TIA or stroke, in those with carotid artery narrowing of 50% or more. Since the trials used to generate our guidelines did not require surgery within two weeks of symptoms, the majority of treated patients underwent surgery well after 2 weeks. This means that the large added benefit of performing surgery early was not captured in these trials and that if this information is 'factored in', many more patients in the 50-69% stenosis group (not just men, not just those with a 5-year or more life expectancy) would likely benefit from it. While this is a theoretical consideration, it certainly enters my mind when I am considering these options with my patients.

A large study (ISAT) finds that clotting brain aneurysms (from the inside) is superior to surgical treatment.

Review:

(As reported by Matthew Fink in the October 2005 issue of Neurology Alert)

Bleeding into the fluid that surrounds the brain (subarachnoid hemorrhage) is often devastating, in terms of neurological damage. Typically the cause of such bleeding is rupture of a ballooned region of brain artery, called an aneurysm. Physicians have devised two main methods of treating a ruptured brain aneurysm. One is surgical clipping (see diagram), which involves opening the cranium, finding the aneurysm, and placing a tight metal clip across its base, cutting it off from the blood supply. Another method of treatment is endovascular coiling (see diagram), during which a fine wire is threaded through the leg artery and up into the aneurysm. A fine coil of wire is then packed into the aneurysm. This coil is coated with a substance that makes blood clot rapidly and the aneurysm subsequently clots off. In the International Subarachnoid Aneurysm Trial (ISAT), 2143 patients were studied, all of whom had suffered from a ruptured intracranial aneurysm and who were felt by treating physicians to be appropriate for either clipping or coiling. Patients were randomized to either treatment and were followed for 1 year to monitor their outcomes. After 1 year, 23.5% of patients undergoing coiling were either dead, or were in a dependent condition (unable to care for themselves). This was statistically better than the outcomes of those undergoing surgical clipping (30.9% in the dead or dependent category). After 4 years, similar results were obtained.

Commentary:

Coiling has clear advantages since there are no major surgical scars (and therefore chances for significant infections), brain damage from the procedure itself is highly unlikely, and seizures secondary to the procedure are unlikely. While the ISAT study lends support to the practice of coiling, the issue is not simple. First of all, surgery itself is not a static practice. There are constantly new techniques and tools being invented to make surgery outcomes better and better. As a result, one can never think that the question of which intervention has been proved more beneficial has been settled once and for all. Surgical clipping also has the advantage of immediately and completely clotting off the aneurysm. As pointed out by Dr. Fink, there may be as many as 66% of coiled aneurysms which are not completely clotted off. If these aneurysms cause recurrent subarachnoid bleeds in the ISAT patients over the next 5 years, coiling may loose its apparent advantage. Finally, the patients selected for this study were felt by treating physicians to be appropriate for both techniques. Some patients (say, those with large and superficial aneurysms) may be more appropriate for surgical clipping and others (those with smaller aneurysms in the brainstem) may be better treated with coiling.

A study finds that Pletal (cilostazol) slows the progression of arterial narrowing in the brain.

Summary:

(As reported in the April 2005 issue of Stroke)

Korean researchers (Kwon et. al) randomized 135 patients who had stroke or TIA symptoms related to narrowing of a major artery of the brain (intracranial arterial stenosis of the middle cerebral artery or basilar artery). Measurement of the degree of narrowing was accomplished using magnetic resonance angiograms and a form of ultrasound called transcranial doppler. All patients were maintained on aspirin, while half of them were placed on Pletal (cilostazol at 200mg per day) and the other half on a placebo. Patients who were thought to have strokes due to blood clots traveling from the neck arteries or the heart were excluded from the study. While 38 patients dropped out of the study before its completion, the rate and reasons for drop-out were similar between treated and placebo groups. No strokes occurred during the 6 month study. In the placebo group, 28.8% of those with arterial narrowing experienced worsening of the narrowing, while only 6.7% of those on Pletal experienced such worsening. In terms of improvement, 15.4% of those on placebo were found to have a decrease in the degree of narrowing while 24.4% of those on Pletal had such a decrease. These positive results in favor of Pletal were found to be highly statistically significant (p=.008).

Commentary:

Atherosclerosis, the process of inflammation and thickening of arterial walls, is a major cause of heart attacks, peripheral vascular disease, and strokes. While prevention is the key to treatment, doctors have also devised other means to directly open or bypass a narrowed artery. Either surgery or angioplasty with stenting have been used to treat peripheral vascular disease, narrowing of the heart's coronary arteries, or narrowing of the carotid arteries in the neck. Unfortunately, arteries in the brain are much more difficult to access. They are not really accessible surgically and angioplasty, applied to the brain's arteries, is only performed either experimentally or under unusual circumstances.

And so, for any patient who has atherosclerotic narrowing of an artery or arteries in the brain, the focus is usually on prevention. Most neurologists will agree that it is best, in these circumstances, to place patients on a statin medication, keep LDL cholesterol below 100mg/dL, attempt to keep blood pressure under 120/80 mm Hg, control blood sugar, and have the patient maintain an ideal weight as well as follow an exercise regimen. The issue of whether or not the blood thinner Coumadin is better than aspirin for these patients was put to rest with results of the WASID trial - which showed no difference between these two treatments; therefore it is reasonable to place a patient on aspirin or another antiplatelet medication (Ticlid, Aggrenox, Plavix).

The results of this study provide initial support for use of a new type of medication to help reduce arterial narrowing in these patients. Pletal (cilostazol) is a phosphodiesterase inhibitor and has the effect both of dilating arteries in the brain and body as well as reducing blood clot formation. I believe a larger study is in order, to prove that the medication not only improves the appearance of arteries on imaging, but reduces the number of strokes in those treated with it.

Stroke Doc

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